While genomic analysis illuminates the blueprints used by organisms to store and propagate information, proteins are the principal active ingredients in the recipe of life. Thus, our ability to understand and engineer complex biological processes hinges on elucidating the structure and function of whole proteomes -- robust technologies to identify and characterize proteins are vital to this effort. Towards this goal, a primary focus of our research is developing new methods of protein analysis. Currently, we're advancing nanopore sensing technology for interrogation of intact protein strands and peptide fragments. This process results in a series of ionic current blockade data that, when combined with machine learning, can be diagnostic of protein/peptide structure at the single-molecule level. This work represents the first steps towards developing the principles of this technology as a general platform for protein and post-translational modification (PTM) identification, and is aimed at achieving the resolution required to fully grasp the complexities of the proteome.

Molecular Memory and Communication Systems for Synthetic Biology and Nanotech

Biology has evolved complex information storage and processing networks through cellular connections and molecules that participate in highly specific interactions, for example through Watson-Crick base pairing of nucleic acids and protein-based molecular recognition. Modern semiconductor-based computing devices, on the other hand, store and transmit information electronically. Thus, a key challenge in designing synthetic bio-nano hybrid systems that simultaneously harness the advantages of both biological and semiconductor-based technologies is in engineering interfaces that allow for real-time communication across disparate components. To address this, we are harnessing aspects of the CRISPR-Cas system in addition to building a toolbox of new molecular parts (that can be used both in-vitro and in-vivo) to store and transmit information in the form of single-molecule addressable molecular barcodes made of DNA and proteins.